School of Medicine

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Current Research and Scholarly Interests
Our lab studies how intricate control of gene expression and cell signaling is regulated on a minute-by-minute basis to give rise to the remarkable diversity of cell types and tissue morphology that form the living blueprints of developing organisms. This research aims to add a new dimension to our understanding of how cells “know” where to go, when to move and differentiate by employing novel technologies that probe these questions at a highly molecular and nanoscale level. Work in the Barna lab is presently split into two main research efforts. The first is investigating “specialized ribosomes” and mRNA translation in control of gene expression genome-wide in space and time during development. This research is opening a new field of study in which fundamental aspects of gene regulation are controlled by ribosomes harboring a unique activity that “select” for specific mRNAs to translate by virtue of unique RNA regulons embedded within 5’UTRs. The second research effort is centered on employing state-of-the-art live cell imaging to visualize cell signaling and cellular control of organogenesis. This research has led to the realization of a novel means of cell-cell communication dependent on a dense network of actin-based cellular extension within developing organs that interconnect and facilitate the precise transmission of molecular information between cells.

Current Research and Scholarly Interests
Function of Hedgehog proteins and other extracellular signals in morphogenesis (pattern formation), in injury repair and regeneration (pattern maintenance). We study how the distribution of such signals is regulated in tissues, how cells perceive and respond to distinct concentrations of signals, and how such signaling pathways arose in evolution. We also study the normal roles of such signals in stem-cell physiology and their abnormal roles in the formation and expansion of cancer stem cells.

Current Research and Scholarly Interests
Dr. Bejerano, co-discoverer of ultraconserved elements, studies the Human Genome. His research focuses on genome sequence and function in both humans and related primate, mammalian and vertebrate species. He is deeply interested in mapping both coding and non-coding genome sequence variation to phenotype differences, and in extracting specific genetic insights from high throughput sequencing measurements, in the contexts of development and developmental abnormalities.

Current Research and Scholarly Interests
The discovery that insulin-producing β-cells can be generated from cell sources within and outside the pancreas is of fundamental importance in terms of developing novel treatment strategies for diabetes. A major caveat to this is our relatively poor understanding of the players involved in this process and the lack of molecular characterization of the ‘converted’ β-cells. This knowledge is key to our success in enhancing this process to its maximum therapeutic potential and efficiency. In this context, recent work has shown that α-cells can be used as a source to generate β-cells under conditions of near-total β-cell depletion in mice. However the molecular mechanisms regulating α-cell identity are unknown. This knowledge would allow us to harness the potential of α-cells to give rise to β-cells in diabetic patients where pancreatic α-cells tend to be in abundant supply within the pancreas. My work in the laboratory has elucidated the role of two genes in maintaining α-cell identity: Dnmt1 and Arx. Dnmt1, a DNA methyltransferase methylates DNA and is involved in gene repression. Arx is a transcription factor that is essential for α-cell specification during embryogenesis. My work demonstrates that conditional in vivo inactivation of Dnmt1 and Arx in adult α-cells causes them to convert into insulin producing β-like-cells demonstrating the necessity of these two factors in maintaining α-cell fate. Further functional characterization of these ‘converted’ cells will elucidate the extent to which α-to- β-cell conversion has occurred in these animals. I am also assessing the individual contributions of Dnmt1 and Arx in maintaining adult α-cell identity.